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Use of bevacizumab in metastatic colorectal cancer: report from the Mexican opinion and analysis forum on colorectal cancer treatment with bevacizumab (September 2009).

Zinser-Sierra JW, Rodríguez-Ramírez S, Villalobos-Valencia R, Ramírez-Márquez M - Drugs R D (2011)

Bottom Line: In patients who have progressed on a bevacizumab-containing regimen, continuation of bevacizumab is significantly associated with an improved survival based on observational cohort studies.In a study of 219 patients, the addition of bevacizumab to FOLFOX was associated with a significant increase in major or complete pathologic response compared with FOLFOX alone.This approach achieves similar efficacy outcomes with reduced toxicity, and investigation of the role of bevacizumab as maintenance therapy is ongoing.

View Article: PubMed Central - PubMed

Affiliation: Instituto Nacional de Cancerologa (INCan), Mexico City, Mexico. juanwzinser@infosel.net.mx

ABSTRACT
Colorectal cancer is one of the most common cancers worldwide, and although associated mortality rates in South American countries are generally among the lowest in the world, they are on the rise. The prognosis of patients diagnosed with metastatic colorectal cancer has improved markedly over the last 12 years, increasing from 5 months with best supportive care to almost 2 years with combination chemotherapy plus bevacizumab. New prognostic and predictive biomarkers have been identified to guide therapy. Prognostic markers indicate patient survival independent of therapy and include disease stage, mutational status, and carcinoembryonic antigen. More recently, predictive markers of treatment outcomes have been identified. The most studied are mutations of the KRAS and BRAF genes, which are associated with resistance to epidermal growth factor receptor-targeted therapy. Tumor blood vessels have a number of structural and functional abnormalities that result in increased tumor vascularity and growth driven by angiogenesis. The anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab, which binds to and neutralizes VEGF-A, has become a central part of the treatment of metastatic colorectal cancer. The addition of bevacizumab to fluorouracil (5-FU)/leucovorin, irinotecan plus bolus 5-FU/leucovorin, or irinotecan plus infusional 5-FU/leucovorin significantly improves the overall survival of patients with previously untreated metastatic colorectal cancer. In addition, a significant increase in overall survival is seen when bevacizumab is added to oxaliplatin plus infusional 5-FU/leucovorin (FOLFOX) in patients with metastatic colorectal cancer who progressed on a non-bevacizumab-containing regimen. Although the majority of studies were performed prior to the identification of KRAS and BRAF as predictive biomarkers, subsequent analysis has shown the benefits of bevacizumab occur independently of the mutational status of these genes. In patients who have progressed on a bevacizumab-containing regimen, continuation of bevacizumab is significantly associated with an improved survival based on observational cohort studies. Surgical resection is recommended in patients with metastatic colorectal cancer where complete removal of tumors can be achieved. Perioperative chemotherapy using FOLFOX for 3 months before and 3 months after surgery is associated with a 9% improvement in 3-year survival. The use of chemotherapy in patients initially deemed unresectable has produced resection rates approaching 40%, and the addition of bevacizumab to chemotherapy in this setting is feasible, safe, and effective. In a study of 219 patients, the addition of bevacizumab to FOLFOX was associated with a significant increase in major or complete pathologic response compared with FOLFOX alone. Improvements in patient survival have changed the treatment paradigm for metastatic colorectal cancer. Newer approaches view treatment not as distinct lines of therapy but as a continuum that includes personalized treatment plans offering maintenance therapy and even drug holidays between aggressive treatment periods. This approach achieves similar efficacy outcomes with reduced toxicity, and investigation of the role of bevacizumab as maintenance therapy is ongoing.

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Median overall survival following first-line treatment for metastatic colorectal cancer.[4–10] 5-FU = fluorouracil; BEV = bevacizumab; FOLFIRI = irinotecan plus infusional fluorouracil/leucovorin; FOLFOX = oxaliplatin plus infusional fluorouracil/leucovorin; IFL = irinotecan plus bolus fluorouracil/leucovorin; LV = leucovorin.
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Fig1: Median overall survival following first-line treatment for metastatic colorectal cancer.[4–10] 5-FU = fluorouracil; BEV = bevacizumab; FOLFIRI = irinotecan plus infusional fluorouracil/leucovorin; FOLFOX = oxaliplatin plus infusional fluorouracil/leucovorin; IFL = irinotecan plus bolus fluorouracil/leucovorin; LV = leucovorin.

Mentions: Twenty-five years ago, few physicians were optimistic about the chances of progress in the treatment of colorectal cancer and for improved survival for patients with this disease. However, over the last decade or so, survival rates of patients with metastatic colorectal cancer have increased from 5 months with best supportive care[4] to almost 2 years with combination chemotherapy with fluorouracil (5-FU), leucovorin plus irinotecan plus bevacizumab (figure 1).[7] Throughout this time, a growing body of evidence has developed to support the importance of vascular and nutritional support for the survival of the tumor, and has ultimately led to the development of agents such as bevacizumab, which work through disruption of tumor blood flow by decreasing angiogenesis. This review is based on a series of meetings of an opinion and analysis panel in Mexico City in September 2009, and discusses a number of important issues in the treatment of colorectal cancer, including the use of prognostic and predictive biomarkers, the optimum treatment of metastatic disease, and resection of hepatic metastases.


Use of bevacizumab in metastatic colorectal cancer: report from the Mexican opinion and analysis forum on colorectal cancer treatment with bevacizumab (September 2009).

Zinser-Sierra JW, Rodríguez-Ramírez S, Villalobos-Valencia R, Ramírez-Márquez M - Drugs R D (2011)

Median overall survival following first-line treatment for metastatic colorectal cancer.[4–10] 5-FU = fluorouracil; BEV = bevacizumab; FOLFIRI = irinotecan plus infusional fluorouracil/leucovorin; FOLFOX = oxaliplatin plus infusional fluorouracil/leucovorin; IFL = irinotecan plus bolus fluorouracil/leucovorin; LV = leucovorin.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585989&req=5

Fig1: Median overall survival following first-line treatment for metastatic colorectal cancer.[4–10] 5-FU = fluorouracil; BEV = bevacizumab; FOLFIRI = irinotecan plus infusional fluorouracil/leucovorin; FOLFOX = oxaliplatin plus infusional fluorouracil/leucovorin; IFL = irinotecan plus bolus fluorouracil/leucovorin; LV = leucovorin.
Mentions: Twenty-five years ago, few physicians were optimistic about the chances of progress in the treatment of colorectal cancer and for improved survival for patients with this disease. However, over the last decade or so, survival rates of patients with metastatic colorectal cancer have increased from 5 months with best supportive care[4] to almost 2 years with combination chemotherapy with fluorouracil (5-FU), leucovorin plus irinotecan plus bevacizumab (figure 1).[7] Throughout this time, a growing body of evidence has developed to support the importance of vascular and nutritional support for the survival of the tumor, and has ultimately led to the development of agents such as bevacizumab, which work through disruption of tumor blood flow by decreasing angiogenesis. This review is based on a series of meetings of an opinion and analysis panel in Mexico City in September 2009, and discusses a number of important issues in the treatment of colorectal cancer, including the use of prognostic and predictive biomarkers, the optimum treatment of metastatic disease, and resection of hepatic metastases.

Bottom Line: In patients who have progressed on a bevacizumab-containing regimen, continuation of bevacizumab is significantly associated with an improved survival based on observational cohort studies.In a study of 219 patients, the addition of bevacizumab to FOLFOX was associated with a significant increase in major or complete pathologic response compared with FOLFOX alone.This approach achieves similar efficacy outcomes with reduced toxicity, and investigation of the role of bevacizumab as maintenance therapy is ongoing.

View Article: PubMed Central - PubMed

Affiliation: Instituto Nacional de Cancerologa (INCan), Mexico City, Mexico. juanwzinser@infosel.net.mx

ABSTRACT
Colorectal cancer is one of the most common cancers worldwide, and although associated mortality rates in South American countries are generally among the lowest in the world, they are on the rise. The prognosis of patients diagnosed with metastatic colorectal cancer has improved markedly over the last 12 years, increasing from 5 months with best supportive care to almost 2 years with combination chemotherapy plus bevacizumab. New prognostic and predictive biomarkers have been identified to guide therapy. Prognostic markers indicate patient survival independent of therapy and include disease stage, mutational status, and carcinoembryonic antigen. More recently, predictive markers of treatment outcomes have been identified. The most studied are mutations of the KRAS and BRAF genes, which are associated with resistance to epidermal growth factor receptor-targeted therapy. Tumor blood vessels have a number of structural and functional abnormalities that result in increased tumor vascularity and growth driven by angiogenesis. The anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab, which binds to and neutralizes VEGF-A, has become a central part of the treatment of metastatic colorectal cancer. The addition of bevacizumab to fluorouracil (5-FU)/leucovorin, irinotecan plus bolus 5-FU/leucovorin, or irinotecan plus infusional 5-FU/leucovorin significantly improves the overall survival of patients with previously untreated metastatic colorectal cancer. In addition, a significant increase in overall survival is seen when bevacizumab is added to oxaliplatin plus infusional 5-FU/leucovorin (FOLFOX) in patients with metastatic colorectal cancer who progressed on a non-bevacizumab-containing regimen. Although the majority of studies were performed prior to the identification of KRAS and BRAF as predictive biomarkers, subsequent analysis has shown the benefits of bevacizumab occur independently of the mutational status of these genes. In patients who have progressed on a bevacizumab-containing regimen, continuation of bevacizumab is significantly associated with an improved survival based on observational cohort studies. Surgical resection is recommended in patients with metastatic colorectal cancer where complete removal of tumors can be achieved. Perioperative chemotherapy using FOLFOX for 3 months before and 3 months after surgery is associated with a 9% improvement in 3-year survival. The use of chemotherapy in patients initially deemed unresectable has produced resection rates approaching 40%, and the addition of bevacizumab to chemotherapy in this setting is feasible, safe, and effective. In a study of 219 patients, the addition of bevacizumab to FOLFOX was associated with a significant increase in major or complete pathologic response compared with FOLFOX alone. Improvements in patient survival have changed the treatment paradigm for metastatic colorectal cancer. Newer approaches view treatment not as distinct lines of therapy but as a continuum that includes personalized treatment plans offering maintenance therapy and even drug holidays between aggressive treatment periods. This approach achieves similar efficacy outcomes with reduced toxicity, and investigation of the role of bevacizumab as maintenance therapy is ongoing.

Show MeSH
Related in: MedlinePlus